Formation,Stability And Application Of Nanoemulsions Prepared By Spontaneous Emulsification Method

Emulsions with droplet size in the nanometric scale?typically less than 200 nm?are often referred to in the literature as nanoemulsions.Due to their characteristics droplet size,nanoemulsions appear transparent or translucent to the naked eye and possess long-term stability against sedimentation or creaming.These properties make nanoemulsions of interest for fundamental researches and practical applications,such as pharmacy,cosmetic,agriculture and chemical systhesis,etc.There are many papers or researches have paid attention to the preparation of nanoemulsions by low-energy method.And the main factors that have effect on the formation and stability of nanoemulsions were also discussed.However,there are still some problems about low-energy methods need to deep further discussed.?1?The mechanism of spontaneous emulsification has been poorly understood;?2?Nanoemulsions have a tendency to breakdown over time,this phenomenon is a result of the concerted action of manifold factors.Nevertheless,we still have little knowledge in controlling the stability of naneomulsions;?3?Measurement of the drug solubility is the mostly used approach for selectingthe components of self-emulsification nanoemulsion?SNEDDS?,but this method is time-consuming and partial.The emulsifying efficiency and stability of nanoemulsions should also be considered during the optimization of formulations;?4?There are fewer reports on the nanoemulsions application in agricultural,especially the relationships between the bioactivity and the ingredients of nanoemulsions;?5?Although norcantharidin?NCTD?have a significant inhibitation on various agricultural insect pests and plant pathogens,the higher dosage of NCTD limited its practical application.NCTD microemulsion of pesticide has been developed,whereas the high content of surfactant was more likely to bring on the side effects.Under such background,this manuscript includes the following sections:1.Preparation of O/W nanoemulsions by spontaneous emulsification methodThe spontaneous emulsification or self-emulsification method?SE?is one important type of low-energy method.Spontaneous nano-emulsification was performed by pouring the oil plus surfactant?with or without cosurfactant?into the mildly stirred aqueous phase.Nanoemulsions were formed immediately.In this section,nanoemulsions containing long-chain fatty acid ester?ethyl oleate?as the oil phase were produced by SE.The type and concentration of surfactant and cosurfactant have effect on the properties of nanoemulsions.The droplet diameter of nanoemulsions decreased as the increasing surfactant concentration and decreasing cosurfactant content.The main factors influencing the properties of nanoemulsions were the critical packing parameter?p?of surfactant and the partition coefficient?Log P?of cosurfactant.Remarkably,there was a linear relation between the Log P of cosurfactant and the droplet size of nanoemulsions?R²=0.8?.In order to investigate the phase behavior during emulsification,the measurement of conductivity,observation by the polarized microscopy and determination of interfacial tension were combined.It was found that the diffusion of hydrophilic components from dispersed phase into aqueous phase converted system to a microemulsion phase that subsequently became supersaturated in oil.As a result,small oil dropletswere nucleated spontaneously from the microemulsion.In addition,the droplet size of nanoemulsions did not significantly change upon dilution with different media.Subsequently,nanoemulsions with different surfactant-to-oil mass ratio?SOR?were prepared by microemulsion dilution method to further explore the mechanism of SE.The results showed that the complete emulsification of the oil phase and converted it into the bicontinuous phase or liquid crystalline phase was the main factors forthe nanoemulsion formation.2.Stability of nanoemulsions produced by spontaneous emulsification methodDue to their small droplet size,nanoemulsions possess kinetically stability and with Ostwald ripening as the main mechamism of nanoemulsion breakdown.In this chapter,measurement of nanoemulsion droplet size,size distribution,Zeta potential,visual observation and linear fitting were employed to investigate the main breakdown process of nanoemulsions prepared by SE.Moreover,the impact of hydrophobic substance addition on the stability of nanoemulsions was also studied.Nanoemulsions are thermodynamically unstable systems.Hence,the final structure and properties of nanoemulsions depends on their components.Ostwald ripening was the major breakdown mechanism at higher surfactant concentration where the presence of micelles can solubilize the oil molecular.Coalescence was identified as the dominant growth process at low surfactant concentration where a decrease in steric and electrostatic repulsion cause the flattening of the hairy layer.In addition,the rate of Ostwald ripening increased as the increasing hydrophilicity of cosurfactant.Both Ostwald ripening and coalescence can cause the droplet size increased with time.A new approach,based on the results of linear fitting and the time evolution of droplet size distribution,was proposed to illustrate the growth mechanism of nanoemulsions.The variation of nanoemulsions droplet size can be related to the governing destabilization mechanism:droplet size increasing can be attributed to both coalescence and Ostwald ripening,whereas droplet size decreasing is a result of Ostwald ripening.3.Selection and optimization of NCTD-loaded SNEDDSBased on the fundamental studies on the formation and stability of nanoemulsion prepared by SE,in this section,we developed,selected and optimized NCTD-loaded SNEDDS.In the first step,the determination condition for GC of NCTD and NCTD-nanoemulsions were optimized and applied for further components selection of SNEDDS and determining NCTD entrapment efficiency.Saturation solubility of NCTD in various oils was determined using the shake flask method to screening the appropriate oil.Selection of surfactant and cosurfactant was primarily governed by their emulsification efficiency,droplet size and size distribution,transmittance and emulsification time.The physical characteristics,such as thermodynamic stability,NCTD loading,cloud point and robustness to dilution were evaluated to optimized the components.As a result,ethyl oleate?50%?,Cremophor EL?35%?and ethylene glycerol?15%?were selected as the components to encapsulate NCTD.The optimized NCTD-SNEDDS withstanding extensive dilution,having good component compatibility and exhibiting long-term stability,would improve the bioavailability of NCTD and could be used for further application.4.Characterization and bioactivity assay of pesticide nanoemulsionsThe continuous phase of nanoemulsions is water,so it can avoid the safety problems caused by the utilization of toluene,dimethylbenzene etc.organic solvent.Moreover,nanoemulsions with low surfactant content that can reduce the side effects.SNEDDS can improve the bioavailability of drugs.Considering the water solubility and high dose of NCTD,we selected the environment-friendly nonionic surfactant-Cremophor EL as the emulsifier and n-butanol as the cosurfactant to prepare nanoemulsions.To compare the insecticidal activity of NCTD and NCTD-SNEDDS,the 3^th-instar larva of Plutella xylostellal was selected.The result of experiment indicated that NCTD-SNEDDS have high bioactivity(24 h,LC₅₀=150.090 mg/L;48 h,LC₅₀=60.414 mg/L)than NCTD suspension.In addition,the concentration of surfactant and cosurfactant play important roles in the activity of NCTD-SNEDDS.